NEW YORK (Reuters Health) - Iron chelation therapy (ICT) with deferasirox led to longer event-free survival in iron-overloaded patients at low-to-intermediate risk of myelodysplastic syndrome (MDS) in a phase 2 study.

"The safety profile of deferasirox was clinically manageable and similar to placebo, except for a non-severe, manageable increase in serum creatinine," Dr. Emanuele Angelucci of San Martino Hospital in Genoa, Italy, told Reuters Health by email. "Most adverse events were likely related to the underlying disease and/or the iron overloaded state of patients."

"As patients with higher-risk MDS have a projected shorter lifespan than lower-risk MDS, and generally require more demanding therapy to change the natural history of their disease, it is less likely that chelation therapy would impact on their survival," he said.

Importantly, the trial protocol was amended from a phase 3 to a phase 2 study due to slow enrollment and follow-up differed between the groups.

As reported in Annals of Internal Medicine, 149 participants were randomized to deferasirox dispersible tablets (10 to 40 mg/kg daily) and 176, to placebo. The primary end point was event-free survival, defined as time from date of randomization to the first nonfatal event related to cardiac or liver dysfunction and transformation to acute myeloid leukemia, or death, whichever occurred first.

The median time on treatment was 1.6 years in the deferasirox group and one year in the placebo group. Median event-free survival was 3.9 years with deferasirox versus three years for placebo (hazard ratio, 0.64).

Dr. Mohammad Maher Abdul Hay, Director, Clinical Leukemia Program, Perlmutter Cancer Center at NYU Langone in New York City, commented in an email to Reuters Health, "Most studies that have investigated ICT in MDS patients are underpowered or retrospective. Furthermore, these patients usually succumb to other pathologies and hence it has been difficult to establish a survival benefit for ICT. Regardless, some hematologists still use ICT for MDS patients when ferritin is above 1,000."

"This study, although underpowered, is interesting in that it is the first randomized trial that attempts to show a benefit for ICT in low-to-intermediate risk MDS," he noted. "Based on our practice, we do not expect ICT to be beneficial in high risk-MDS patients given their short overall survival. As we develop more targeted treatment for MDS patients, including (those at) high-risk, ICT may then play a role."

The study was funded by Novartis. Dr. Angelucci and three coauthors have received fees from the company.

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